Induction of protection in mice against a respiratory challenge by a vaccine formulated with the Chlamydia major outer membrane protein adjuvanted with IC31®

Cheng, Chunmei; Cruz-Fisher, Maria I.; Tifrea, Delia F.; Pal, Sukumar; Wizel, Benjamin; Maza, Luis M. de la

doi:10.1016/j.vaccine.2011.01.031

Cited by 13 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results can likely be explained by the capacity of IC31 to signal through TLR9/MyD88 and induce dendritic cell maturation, which is thought to then be responsible for driving Th1 responses [30]. The different cellular distribution of TLR9 in mice and humans has historically posed a problem with results gained from mouse models not translating into humans [31].…”

Section: Discussionmentioning

confidence: 91%

“…Moreover, the induction of CD8+ T-cell memory at a mucosal site, and specifically in the gut, is likely to be important in preventing HIV replication early after infection. This effect on mucosal immunity might be one of the causes for the protection from Chlamydia infection in a recent vaccination study where IC31 was used as the adjuvant [30].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity

et al. 2012

Self Cite

View full text Add to dashboard Cite

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…A random survey of very recently published papers in which intranasal instillation was employed for delivery of infectious agents (bacterial and fungal pathogens) to the lungs of mice revealed that researchers used a wide range of dose volumes in combination with a variety of anesthesia types as follows: i) 20 µl instillation volume under pentobarbital [28] or ketamine/xylazine anesthesia [29], [30], [31], [32], [33], ii) 25 µl instillation volume under either pentobarbital [34] or ketamine/xylazine anesthesia [35], iii) 30 µl instillation volume under ketamine/xylazine anesthesia [36], iv) 35 µl instillation volume under ketamine/xylazine anesthesia [37], v) 40 µl instillation volume under isoflurane anesthesia [38], vi) 50 µl instillation volume under either ketamine/xylazine [39], isoflurane [40], [41], [42], [43], [44], halothane [45], [46], and vii) 100 µl instillation volume under isoflurane anesthesia [47]. Moreover, a number of recent papers either supplied information regarding the dose volume used without indicating the type of anesthesia [48], [49], indicated the anesthesia used but failed to indicate the dose volume [50], [51], or supplied no information regarding either the dose volume or anesthesia [52], [53], [54] used for intranasal instillation.…”

Section: Discussionmentioning

confidence: 99%

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

et al. 2012

View full text Add to dashboard Cite

Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

show abstract

“…So far CpG appear to be the most effective adjuvant for inducing a protective immune response in animals against a chlamydial challenge [21–24]. Here, to determine if other types of adjuvants can be more effective than CpG, we screened several TLRs and NODs agonist for their ability to adjuvantivize a vaccine formulated with a Chlamydia rMOMP.…”

Section: Introductionmentioning

confidence: 99%

A TLR2 agonist is a more effective adjuvant for a Chlamydia major outer membrane protein vaccine than ligands to other TLR and NOD receptors

Cheng

Jain

Bettahi

et al. 2011

Vaccine

Self Cite

View full text Add to dashboard Cite

Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial pathogen in the World and there is an urgent need for a vaccine to prevent these infections. To determine what type of adjuvant can better enhance the immunogenicity of a Chlamydia vaccine, we formulated the recombinant major outer membrane protein (Ct-rMOMP) with several ligands for Toll-like receptor (TLR) and the nucleotide-binding oligomerization domain (NOD) including Pam2CSK4 (TLR2/TLR6), Poly (I:C) (TLR3), monophosphoryl lipid A (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), imidazoquinoline R848 (TRL7/8), CpG-1826 (TLR9), M-Tri-DAP (NOD1/NOD2) and muramyldipeptide (NOD2). Groups of female BALB/c mice were immunized intramuscularly (i.m.) three times with the Ct-rMOMP and each one of those adjuvants. Four weeks after the last immunization the mice were challenged intranasally (i.n.) with 104 C. trachomatis mouse pneumonitis (MoPn) inclusion forming units (IFU). As negative antigen controls mice were immunized with the Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) and the same adjuvants. As a positive vaccine control mice were inoculated i.n. with 104 IFU of MoPn. The humoral and cell mediated immune responses were determined the day before the challenge. Following the challenge the mice were weighed daily and, at 10 days post-challenge (p.c.), they were euthanized, their lungs weighted and the number of IFU in the lungs counted. As determined by the IgG2a/IgG1 ratio in the sera, mice immunized with Ct-rMOMP + Pam2CSK4 showed a strong Th2 biased humoral immune response. Furthermore, these mice develop a robust cellular immune response with high Chlamydia-specific T cell proliferation and levels of IFN-γ production. In addition, based on changes in body weight, weight of the lungs and number of IFU recovered from the lungs, the mice immunized with Ct-rMOMP + Pam2CSK4, were better protected against the i.n. challenge than any group of mice immunized with Ct-rMOMP and the other adjuvants. In conclusion, Pam2CSK4 should be evaluated as a candidate adjuvant for a C. trachomatis vaccine.

show abstract

Induction of protection in mice against a respiratory challenge by a vaccine formulated with the Chlamydia major outer membrane protein adjuvanted with IC31®

Cited by 13 publications

References 45 publications

A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity

A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

A TLR2 agonist is a more effective adjuvant for a Chlamydia major outer membrane protein vaccine than ligands to other TLR and NOD receptors

Contact Info

Product

Resources

About